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Neenu V. Kuzhikandathil et al / Int. J. Res. Ayurveda Pharm. 7(5), Sep - Oct 2016

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Research Article www.ijrap.net

A CLINICAL STUDY TO EVALUATE THE EFFECT OF KRIMIMUDGARA RASA IN MANAGEMENT OF

KRIMIROGA WITH REFERENCE TO INTESTINAL HELMINTHIASES Neenu V. Kuzhikandathil 1, Sreejith Satheesan 2*, Sudharmini S 3

1PG Scholar, Department of PG Studies in Kaumarabhritya, Alva’s Ayurveda Medical College, Moodbidri, Karnataka, India

2Assistant Professor, Department of Shalyatantra, Dharma Ayurveda Medical College, Sriperumbudur, Tamil Nadu, India

3Rtd. Associate Professor of Entomology, Department of Community Medicine, Government Medical College, Thiruvananthapuram, Kerala, India

Received on: 04/07/16 Revised on: 07/09/16 Accepted on: 16/09/16

*Corresponding author E-mail: [email protected] DOI: 10.7897/2277-4343.075197 ABSTRACT The present study was undertaken to evaluate the efficacy of Krimimudgara Rasa, adapting Samshamana as the line of management of krimiroga (helminthiases)in children, described by Acharya Charaka. A simple randomized controlled clinical trial was conducted among 40 randomly selected children of 6-12 years age, suffering from krimiroga and at least showing the symptom Udarashoola (abdominal pain) and presence of ova/cysts/worms of intestinal helminthes on microscopic stool examination. Krimimudgara Rasa 100mg (trial drug) was administered to20 such children. Another set of 20 children were administered with Mebendazole 100mg (control drug).All children were subjected to clinical examination for signs and symptoms and parasite positivity, before treatment, on 7th day and 14th day after treatment. Krimimudgara Rasa and Mebendazole have produced almost same level of reduction of signs and symptoms in patients of both groups. There was no significant difference in the rate of reduction of clinical symptoms, as all the p-values of Unpaired t-test were >0.01.Patients of both groups became completely asymptomatic and negative for ova/cysts of worms on 14th day of treatment. The study has proved the efficacy and safety level of the trial drug and has established that Krimimudgara Rasa is found to be an effective safe alternative anthelminthic drug for soil transmitted intestinal helminthiases. Keywords: Krimiroga, Helminthiases, Krimimudgara rasa, Mebendazole, Anthelminthic drug. INTRODUCTION Helminthiasis is infestation with one or more intestinal parasitic worms like Round worm (Ascaris lumbricoides), Whip worms (Trichuris trichiura) or Hook worms (Necator americanus and Ancylostoma duodenale)1.World Health Organization (W.H.O) considers pre-school and school aged children as high risk population2 for soil transmitted intestinal helminthes. Hence the agency has recommended for deworming once in every six months for every individual in childhood period. But many anthelminthic drugs used have developed resistance and have side effects like toxic or allergic reactions. Several herbal as well as herbo-mineral formulations in Ayurveda are described for the treatment of worm infections. But there is no clinical evidence about their efficacy and safety. Therefore Ayurvedic researches in this particular context can aid to achieve the global target3 of W.H.O to eliminatemorbidity due to soil transmitted helminthiases of children by 2020. Samshamana4 (palliation)is one among the line of management of Krimiroga according to Acharya Charaka which is easier to be administered in children. Krimimudagara Rasa mentioned in Yogaratnakara5 being a rasa preparation, is potent-enough for short term administration which is comparable to that of Albendazole and Mebendazole in modern medicine. Moreover, all the ingredients of this yoga namely, Rasa6 (purified mercury), Gandhaka7 (purified sulphur), Ajamoda8 (Trachyspermum roxburghianum), Vidanga9 (Embelia ribes), Vishamushtika/ Kupeelu10 (Strychnos nux-vomica) and Palasa beeja11 (Butea monosperma)are said to have Krimighna (anthelminthic)

property. This study has evaluated the efficacy of Krimimudgara Rasa in the management of Krimiroga especially intestinal helminthiases, during the months of October-November 2015. MATERIALS AND METHODS In this clinical study the diagnostic criteria of Krimiroga and its treatment modality were assigned with reference to the classical literature from Ayurvedic and Allopathic Medicines. The diagnostic criteria included children having Udarashoola (abdominal pain) in association with two or more general features of Krimi12 namely, Bhakthadwesha (aversion to food), Sadana (exhaustion), Jwara (fever), Vivarnatha (discoloration), Gudakandu (anal itching) and presence of ova/cysts/worm of Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Ancylostoma duodenale or Enterobius vermicularis, in microscopic stool examination. The drugs usedin the study were Krimimudgara Rasa 100mg tablet (trial drug) and Mebendazole 100mg tablet (control drug). Krimighna property of the Krimimudga Rasa is also mentioned in Rasashastra classics like Rasakamadhenu13, Rasa Jala Nidhi14, Rasendra Sara Sangraha15 and Bhaishajyaratnavali16. Shodhana (purification) of all the six ingredients and preparation of 100mg tablet of Krimimudgara Rasa was carried out as per the methods adopted for its standardization and quality control17 of the formulation. The trial drug was prepared in the pharmacy facility of Nangelil Ayurveda Pharmacy, Kothamangalam, Ernakulam, Kerala.


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The control drug used in this study i.e.:100 mg tablet of Mebendazole or (5-benzoyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester) belongs to the organic compounds benzophenones. It is a synthetic broad-spectrum anthelminthic used in the treatment of intestinal helminths18. This drug required for the study was procured from pharmacist’s counters. Study Design and Sampling The Simple Randomized Controlled Clinical Trial19 (RCT) was the study design adopted to envisage the present research work. The study population was from among those children who attended the Kaumarabhritya out-patient department of Alva’s Ayurveda Medical College Hospital, Moodbidri, Karnataka, India and from health camps conducted among schools in and around Koothattukulam and Elanji, Ernakulam District, Kerala, India. A total of 40 children suffering from Krimiroga (infested with either Round worm, Whip worm, Hookworm or Pin worm) and fulfilling the inclusion criteria were randomly selected as study subjects. They were assigned into two groups: Group-A (control) and Group-B (trial), each group with 20 children who were recruited strictly adhering to the guidelines of Indian Council of Medical Research (ICMR)20 and International conference of Harmonization - Good Clinical Practices Guidelines (ICH-GCP)21 with Institutional Ethical Committee Clearance (No. 25/96/2010-AWD dated 20/12/2012). Inclusion Criteria · Children of age group between 6-12 years irrespective of

sex, religion, socio-economic status and food habits. · Children having Udarashoola in association with two or

more symptoms of Krimi. · Children diagnosed with infestation of Ascaris lumbricoides,

Trichuris trichiura, Necator americanus, Ancylostoma

duodenale and/or Enterobiu svermicularis by microscopic stool examination.

Exclusion Criteria · Ascaris infestation with complication such as intestinal

obstruction, pulmonary eosinophilia, cholecystitis and pancreatitis22.

· Microscopic stool examination positive to ova, cyst, or larval forms of intestinal protozoans (Entamoeba hystolitica, Entamoeba coli, Giardia lamblia); Tape worms (Taenia solium, Taenia saginata, Echinococcus granulossus); and also Filarial worms (Wuchereria bancrofti, Brugia malayi).

Administration of Drug and Observation of Patients Each child of control group (Group-A) was given one tablet of Mebendazole 100mg, twice daily for 3 consecutive days. In the trial group (Group-B) each child was given one tablet of Krimimudgara Rasa 100mg, twice daily for 3 consecutive days. Before starting the administration of the drugs, all the children of both the study groups were subjected to clinical examination. Subjects were further examined for clinical symptoms on 7th day after treatment. Follow up was done on 14th day after drug administration (i.e. 2 weeks after treatment) and all the subjects of both groups were observed for any clinical symptoms. Laboratory Investigation

Stool samples of the subjects were examined23 before starting treatment, and after 7thand 14th day of treatment. Collection and Recording of Data A pre-tested proforma was used to record the observations according to assessment criteria. Approximate grading was given for the variables in assessment criteria to correctly evaluate the outcome. Axillary temperature24 was taken to record fever25 of the patients.

Table 1: Grading for the assessment parameters of the study

Udarashoola Bhaktadwesha Sadana Gudakandu Presence of Ova/Cyst/Worm 0 – Absent 1 – Present

0 – Absent 1 – Present




Jwara25 Vivarnatha 0 – Normal Body Temp. [36.1 - 37.2ºC] or [97 - 99ºF] 1 – Fever [>37.5 or 38.3ºC] or [99.5 or 100.9ºF] 2 – Hyperthermia [>38.3 or 39.4ºF] or [101 – 103ºF] 3 – Hyperpyrexia [>40 or 41.5ºC] or [>104 or 106.7ºF]

0 – Absent [Normal skin] 1 – Mild [Only on face] 2 – Moderate [Any half of the body] 3 – Severe [All over body, distinct patches]

Analysis of Data The data collected according to the assessment criteria were analysed using Student’s t-test. Paired t-test was done to find out the effect of drug after treatment within a same group. Unpaired t-test was applied to compare the effects of the two drugs, between control and trial groups. The outcome measurements of the study were calculated as the mean score of symptoms between before treatment and 7thand 14thday after treatment. RESULTS All the 40 children subjected to clinical trial had Udarashoola (abdominal pain)as a major sign and symptom of Krimiroga (helminthiasis)and all were found positive to ova/cyst when stool samples were examined prior to drug administration. Other signs and symptoms complained by them included Vivaranatha (97.5%), Bhaktadwesha (95%) Sadana (85%), Gudakandu (37.5%) and Jwara (22.5%). Stool sample examinationrevealed that the subjects were infected with Enterobius vermicularis (37.5%), Ascaris lumbricoides (20%), Trichuris trichiura

(17.5%), Ancylostoma duodenale (15%) and Necator americanus (10%). The p-values of the paired t-test for the symptoms excepting Jwara (fever) and Gudakandu (anal itching) remained <0.01. Hence the decrease in mean scores of these symptoms is found to be statistically highly significant. Decrease in the mean score of Jwara noticed among the patients treated with Mebendazole (Table 2) was found to be statistically significant as the p-values were <0.05. But among those treated with Krimimudgara Rasa (Table 3), they became symptom-free only on 14th day of treatment. The decrease in mean score of Jwara noticed on 7th

day of treatment is not significant as p-value is >0.05.Patients of control and trial groups were noticed to have decrease in Gudakandu by one week after treatment, but this reduction was not statistically significant as the p-value of paired t-test was >0.01. Results of the unpaired t-test applied to make a comparison of the effect of treatment between Group-A and Group-B on 7thday (Table 4) using the mean difference of before treatment and 7th


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day after treatment (BT-7D) showed that the p-values for criteria Udarashoola (abdominal pain), Bhakthadwesha (aversion to food), Sadana (exhaustion), Jwara (fever), Vivarnata (discolouration), Gudakandu (anal itching) and Presence of ova/cysts/worms in microscopic stool examination are > 0.01. Hence the difference observed between the mean values of all the criteria appear to be statistically not significant while

comparing the effects of the two drugs on the 7th day after treatment. Similar results were obtained while unpaired t-test was applied to compare the effects of treatment between Group-A and Group-B on 14th day (Table 5).The unpaired p-values of the assessment criteria were >0.01.

Table 2: Effect of Mebendazole on Assessment Criteria (Group – A)

Mean of

BT Mean of Mean

difference % Paired ‘t’

SD SE t value P - value Udarashoola

1 7 D 0.30 0.700 70 0.470 0.105 6.658 < 0.0001 1 14 D 0.10 0.900 90 0.307 0.068 13.077 < 0.0001

Bhaktadwesha 0.95 7 D 0.30 0.650 68.42 0.489 0.109 5.940 < 0.0001 0.95 14 D 0.10 0.850 89.47 0.366 0.081 10.376 < 0.0001

Sadana 0.95 7 D 0.25 0.700 73.68 0.470 0.105 6.658 < 0.0001 0.95 14 D 0.10 0.850 89.47 0.366 0.081 10.376 < 0.0001

Jwara 0.35 7 D 0.05 0.300 85.71 0.470 0.105 2.854 0.0102 0.35 14 D 0 0.350 100 0.587 0.131 2.666 0.0153

Vivarnatha 1.55 7 D 0.65 0.900 58.06 0.307 0.068 13.077 < 0.0001 1.55 14 D 0.15 1.400 90.32 0.502 0.112 12.457 < 0.0001

Gudakandu 0.40 7 D 0.25 0.150 37.50 0.366 0.081 1.831 0.0828 0.40 14 D 0 0.400 100 0.502 0.112 3.559 0.0021

Presence of Ova/ Cysts/ Worms 1 7 D 0.35 0.650 65 0.489 0.109 5.940 < 0.0001 1 14 D 0.10 0.900 90 0.307 0.068 13.077 < 0.0001

BT – Before treatment; 7D – 7th day after treatment; 14D – 14th day after treatment; SD – Standard Deviation; SE – Standard Error

Table 3: Effect of Krimimudgara Rasa on Assessment Criteria (Group – B)

Mean of BT

Mean of Mean difference

% Paired ‘t’ SD SE t value P - value

Udarashoola 1 7 D 0.25 0.750 75 0.444 0.099 7.550 < 0.0001 1 14 D 0.20 0.800 80 0.410 0.091 8.718 < 0.0001

Bhaktadwesha 0.95 7 D 0.20 0.750 78.94 0.444 0.099 7.550 < 0.0001 0.95 14 D 0.15 0.800 84.21 0.410 0.091 8.718 < 0.0001

Sadana 0.75 7 D 0.30 0.450 60.00 0.510 0.114 3.943 0.0009 0.75 14 D 0.05 0.700 93.33 0.470 0.105 6.658 < 0.0001

Jwara 0.20 7 D 0.10 0.100 50 0.447 0.100 1.000 0.3299 0.20 14 D 0 0.200 100 0.523 0.117 1.710 0.1036

Vivarnatha 1.55 7 D 0.75 0.800 51.61 0.410 0.091 8.718 < 0.0001 1.55 14 D 0.20 1.350 87.09 0.587 0.131 10.283 < 0.0001

Gudakandu 0.35 7 D 0.20 0.150 42.85 0.366 0.081 1.831 0.0828 0.35 14 D 0 0.350 100 0.489 0.109 3.199 0.0047

Presence of Ova/ Cysts/ Worms 1 7 D 0.45 0.550 55 0.510 0.114 4.819 0.0001 1 14 D 0.20 0.800 80 0.410 0.091 8.718 < 0.0001

BT – Before treatment; 7D – 7th day after treatment; 14D – 14th day after treatment; SD – Standard Deviation; SE – Standard Error


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Table 4: Comparison of Effects of Treatment Between Group - A and Group - B on 7th day

Assessment Criteria

Mean of BT – 7D

Mean Difference

Standard Deviation

t-value Unpaired p-value

Group A Group B Group A Group B Udarashoola 0.70 0.75 0.500 0.470 0.444 0.345 0.7315

Bhaktadwesha 0.65 0.75 0.100 0.489 0.444 0.676 0.5027 Sadana 0.70 0.45 -0.250 0.470 0.510 1.611 0.1154 Jwara 0.30 0.10 -0.200 0.470 0.447 1.378 0.1761

Vivarnata 0.90 0.80 -0.100 0.307 0.410 0.871 0.3888 Guda Kandu 0.15 0.15 0.000 0.366 0.366 0.000 >0.9999

Presence of Ova/ Cyst/ Worms

0.65 0.55 -0.100 0.489 0.510 0.632 0.5309

BT – Before treatment; 7D – 7th day after treatment; Group-A – Control; Group-B – Trial

Table 5: Comparison of Effects of Treatment Between Group-A and Group-B on 14th day

Assessment Criteria

Mean of BT – 14D

Mean Difference

Standard Deviation

t-value Unpaired p-value

Group A Group B Group A Group B Udarashoola 0.90 0.80 -0.100 0.307 0.410 0.871 0.3888

Bhaktadwesha 0.85 0.80 -0.050 0.366 0.410 0.406 0.6867 Sadana 0.85 0.70 -0.150 0.366 0.470 1.125 0.2675 Jwara 0.35 0.20 -0.150 0.587 0.523 0.853 0.3990

Vivarnata 1.40 1.35 -0.050 0.502 0.587 0.289 0.7739 Guda Kandu 0.40 0.35 -0.050 0.502 0.489 0.318 0.7517

Presence of Ova/ Cyst/ Worms

0.90 0.80 -0.100 0.307 0.410 0.871 0.3888

BT – Before treatment; 14D – 14th day after treatment; Group-A – Control; Group-B – Trial DISCUSSION In this clinical study the most common parasitosis of patients was due to Enterobius vermicularis (pin worms) followed by Ascarisand Hookworms. Though the life span of the pinworms is brief, longstanding infections occur due to continuous reinfection26. In addition to the presence of abdominal pain, other major clinical symptoms like aversion to food, discolouration and exhaustion were observed in majority of the children. These clinical findings also get support from samprapti (pathogenesis) proposed for Krimiroga27. The present study revealed that the signs and symptoms due to worm infestation among the children were significantly reduced by the effects of treatment with trial drug (Krimimudgara Rasa) and control drug (Mebendazole). Both these drugs were found to be equally effective in decreasing the symptoms Udarashoola, Bhaktadwesha and Sadana. Due to Shoolaghna (analgesic) property of Ajamoda (Trachyspermum roxburghianum) and Vidanga (Embelia ribes) present in Krimimudgara Rasa, worms are made immobile and dead later, which are gradually eliminated, thereby reducing the pain. This drug has Krimighna28 (anthelminthic), Kandughna, Shoola Prashamana (analgesic), Deepana28 (stomachic) as well as Pachana28

(digestive) properties owing to its ingredients. All the contents are helpful in increasing digestive power by improving Agni and also creating a hostile environment inside the gastro intestinal tract (GIT), later removing the parasites and reducing the symptoms of Krimiroga. Strychnine and Embeline are the characterising compounds which are biologically or therapeutically active principles in Krimimudgara Rasa29. Strychnine strengthens the muscles of stomach and expels worms from the body. Embeline is responsible for anthelminthic activity exhibited by this drug. In the case of control drug, it is established that the principal mode of action for Mebendazole30 is by its inhibitory effect on tubulin polymerization, which results in decreased production of adenosine triphosphate (ATP). Due to diminished energy production, the parasites are immobilized and eventually die. In

the light of these modes of actions of both the drugs, it is also understood that the effects of trial drug and control drug were almost similar in reducing clinical symptoms and decreasing parasitic load in stool samples of treated patients. Effect of Krimimudgara Rasa in reducing Jwara (fever) was not found satisfactory on 7th day after treatment, even though the drug produced good effect on 14thday of treatment. In contrast, the drug Mebendazole could make a significant reduction in Jwara (fever) from before treatment to 7th and 14thday after treatment. Gudakandu (anal itching) was persisting among patients of both groups still on 7thday of treatment. All those patients became symptom-free on 14thday of treatment only. This could be due the fact that in pinworm infection, adult female worm31,32 oviposits around 11,000 to 16,000 eggs at a time at the perianal region resulting in autoinfection. This leads to more new generations of young worms which are also resistant33, 34 to drugs. As the unpaired t-test showed no significant difference between the effects of treatment among children administered with Mebendazole and Krimimudgara Rasa, it can be inferred that the trial drug (Krimimudgara Rasa) is also effective as the control drug (Mebendazole), which is an established anthelminthic drug recommended by WHO. CONCLUSION Treatment with Krimimudagra rasa has produced striking effects in reducing all the clinical symptoms assessed in the study except fever. The trial drug also proved beneficial in eliminating the ova/cysts/worms of helminths which was evident in microscopic stool examination. These findings also established that Samshamana (palliative) method is also effective in treating Krimiroga, which has been described by Acharya Charaka along with Apakarshana(extraction), Prakriti Vighata (disruption of pathogenesis), Nidana Parivarjana (avoiding causative factors) and Samshodhana (evacuation of doshas). Since no significant difference was noticed in the unpaired t-test between the effects of treatments with Krimimudgara Rasa and Mebendazole, it can


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be inferred that Krimimudgara Rasa (trail drug) is found to be as effective as Mebendazole (control drug) in treating Krimiroga. The trial drug is also found to be absolutely free from any sort of side effects or adverse reactions in its therapeutic dose and duration. Thus the present clinical study proves that Krimimudgara rasa can be used as a safe and effective alternative anthelminthic drug for soil-transmitted intestinal helminthiases. It can also be used therapeutically for short durations just like the well-established anthelminthic drug Mebendazole. ACKNOWLEDGEMENT The authors gratefully acknowledge the Managing Director, Nangelil Ayurveda Medical College, Ernakulam, for the permission to utilize the pharmacy facility for the preparation of the trial drug. REFERENCES 1. www.who.int/topics/helminthiasis/en; © WHO, [updated

2014 March 3; cited 2015 June 2] 2. www.who.int/intestinal_worms/strategy/en; © WHO,

[updated 2014 March 3; cited 2015 June 2] 3. www.who.int/mediacentre/factssheets/fs366/en; ©WHO,

[updated 2014 March 3; cited 2015 June2] 4. Agnivesa, Charaka Samhitha; Ayurveda Deepika

commentary by Chakrapanidatta; edited by Jadavaji Trikamaji Acharya; Chaukambha Prakashan,Varanasi; Ed. Reprint; Vimanasthana; Ch. 7; Slokka 28-30; pp.26; 2011

5. Yogaratnakara; edited and translated by Babu, Madham Shetty Suresh; Choukhamba Sanskrit Series Office, Varanasi; Ed. 1; ISBN: 81-7080-1494; Purvardham – Vol. I; pp.413; 2005

6. Singh, Ramaadarsha; Rasendravijnanam; Sanjeevani Nirmanshala, Saran (Dist.), Bihar; Ed.1st, 1965, Ch. 1, Rasavijnaneeya adhyaya, pp.13

7. Singh, Ramaadarsha; Rasendravijnanam; Sanjeevani Nirmanshala, Saran (Dist.),Bihar; Ed.1st, Ch. 2, Uparasavijnaneeya adhyaya, pp.82; 1965

8. Bhavamisra; Bhavaprakasha Nighantu; commentary by K.C. Chunekar; edited by G.S. Pandey; Chaukhamba Bharati Academy, Varanasi; Ed. Reprint; 2010, pp. 26

9. Bhavamisra; Bhavaprakasha Nighantu; commentary by K.C. Chunekar; edited by G.S. Pandey; Chaukhamba Bharati Academy, Varanasi; Ed. Reprint; 2010, pp.50



12. Sushruta, Sushruta Samhitha; edited by K.R Srikantha Murthy; Chaukhambha Orientalia, Varanasi; Ed. 2, 2005; Sutrasthana, Vol. III, Ch.54, Shloka 16-19, pp.357

13. “Rasakamdhenu”; compiled by Vaidyavara Sri Chudamani; revised by Rasavaidya Jivaram Kalidas Shastry; Chaukambha Publishers, Varanasi; 2001, Ch. 20, pp. 246.

14. “Rasa Jala Nidhi”; Mookerjee, Bhudeb; Chaukhambha Publishers, Varanasi; Ed.4, 2004, Vol.V; Ch. Krimirogadhikara; pp.200.

15. Bhatt, Gopal Krishna; “Rasendra Sara Sangraha”; edited by Suresh, Parimi; Dhannaapuneni, Vinaya Kumari; Chaukhambha Sanskrit Sansthan, Varanasi; Ed.1; 2007; Ch. Krimichikitsa; Shloka 14-15; pp. 425; ISBN: 978-81-89798-05-5

16. Govindadas; “Bhaishjyaratnavali”, commentary by Shastri, Venimadhav Ashwani Kumar; Chaukhambha Krishnadas

Academy, Varanasi; Ed.1; 2008; Ch. Krimyadhikara; Shloka 19; pp. 221.

17. Nakve Amruta P, Rai Pallavi D, Deokate Uday A, Khadabadi Somashekhar S; “Standardization and Quality Control Evaluation of Krimimudgara Rasa using Microscopic Studies and HPTLC”, International Journal Of Pharmacy & Technology; March 2011, Vol. 3, Issue No.1, Pp. 1537-1547

18. Keiser, J; Utzinger, J (2010). “The drugs we have and the drugs we need against major helminth infections”, Advances in parasitology 73: 197–230. doi:10.1016/s0065-308x(10)73008-6. PMID 20627144.

19. Park, K; Park’s Textbook of Preventive and social Medicine; published by M/s Banarasidas Bhanot, Jabalpur, Ed. 18, Jan.2005; Ch. 3; pp. 75-79.

20. ICMR (2000). Ethical Guidelines for Biomedical Research on Human Subjects, Indian Council for Medical Research, Government of India, New Delhi, pp.25-33.

21. ICH-GCP, Integrated Addendum to ICH E6 (R1): Guideline for Good Clinical Practice; ICH Steering Committee, Current Step 2 version; 11 June, 2015.

22. Nelson Textbook of Pediatrics; edited by Kliegman, Behrman, Jenson, Stanton, Reed; published by Elsevier India Pvt. Ltd., New Delhi; Ed. 18; Vol. I; Ch. 288; pp.1495

23. Director General of Health Services, Ministry of Health and Family Welfare, Govt. of India; ‘Manual for the Laboratory Technician at the Primary Health Centre’, 1985, Adapted by permission from the ‘Manual of Basic Techniques for a Health Laboratory’, by Etienne Levy-Lambert, WHO 1980; Ch.8, pp.95-99.

24. Barton D. Schmitt, J. Todd Jacobs; Instructions for Pediatric Patients; Published by Saunders, Ed. 2(revised), 1999; ISBN-13: 978-0721678856.

25. Sajadi MM, Mackowiak PA. Temperature regulation and the pathogenesis of fever”, In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases; 8th ed. Philadelphia, PA: Elsevier Saunders, Ch. 55; 2015.

26. John E. Bennett, Raphael Dolin, Martin J. Blaser; Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Elsevier Health Sciences; Ed. 8, 2014; Ch. 288, Part III, pp. 3206.

27. Harita Samhitha; edited by Jaymini Pandey; Chaukhambha Visvabharati, Varanasi; Ed. 1, 2010; Tritiya sthana, Ch. 5, Shloka 18-21, pp. 253

28. Nisha Raj, Subrahmanya P, Ravi Rao S, Mahesh TS, Sridevi Joshi. A Clinical Study of Combretum extensum Roxb. with special reference to its Krimighna Effect. Int. J. Res. Ayurveda Pharm 2012;3(2):177

29. Rajiv Kukkar, A.K.Saluja, U.D.Shah, Mona R.Kukkar; Estimation of Embelin And Strychnine in Krimimudgara Rasa by HPTLC Method, International Journal of Pharmaceutical Quality Assurance; January-March 2010, Vol 2, Issue 1, pp. 3.

30. Lubega GW, Geary TG, Klein RD, Prichard RK; Expression of cloned beta-tubulin genes of Haemonchus contortus in Escherichia coli: interaction of recombinant beta-tubulin with native tubulin and Mebendazole, Mol Biochem Parasitol; 1993 Dec; 62(2):281-92

31. Gutiérrez, Yezid (2000), Diagnostic pathology of parasitic infections with clinical correlations, Ed. 2, Oxford University Press. pp. 354–366,

32. Burkhart CN, Burkhart CG (October 2005), Assessment of frequency, transmission, and genitourinary complications of enterobiasis (pinworms), International Journal of Dermatology 44 (10): 837–40.


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33. Cho SY, Kang SY, Kim SI, et al., Effect of anthelmintics on the early stage of Enterobius vermicularis, Kisaengchunghak Chapchi. June 1985. 23:7-17.

34. Hong ST, Cho SY, Seo BS et al. Chemotherapeutic control of Enterobius vermicularis infection in orphanages, Kisaengchunghak Chapchi. June 1980. 18:37-44.

Cite this article as: Neenu V. Kuzhikandathil, Sreejith Satheesan, Sudharmini S. A clinical study to evaluate the effect of krimimudgara rasa in management of krimiroga with reference to intestinal helminthiases. Int. J. Res. Ayurveda Pharm. Sep - Oct 2016;7(5):64-69 http://dx.doi.org/10.7897/2277-4343.075197

Source of support: Nil, Conflict of interest: None Declared

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